: The greatest uncertainties contributing to poor confidence in risk assessments for water disinfection by-products (DBPs) stem from inadequacies in our capability to determine the relevancy to humans of results from experiments using rodents. The need for data and approaches to address this issue is manifold and includes all aspects of rodent to human extrapolation. Significant data gaps remain in this area for the most prevalent DBPs in our drinking water, the trihalomethanes (THMs). While some progress has been made with chloroform (CHCl3), human data fro brominated THMs (BrTHMs) is nonexistent. For example, in order to scale up existing rodent THM physiologically-based pharmacokinetic (PBPK) models for humans, in vitro determinations of THM metabolic rates are needed. It is also essential to determine if the same metabolic pathways are operative in rodents and humans and if metabolic flux through the different pathways is similar.